Apoptosis of human breast cancer cells induced by microencapsulated betulinic acid from sour jujube fruits through the mitochondria transduction pathway

Food Chem. 2013 Jun 1;138(2-3):1998-2007. doi: 10.1016/j.foodchem.2012.10.079. Epub 2012 Nov 15.

Abstract

Betulinic acid (BA), a natural pentacyclic triterpenoid, was isolated from sour jujube fruits for the first time. An inclusion complex comprising BA and β-cyclodextrin (β-CD) was formed to improve the dissolution of BA, but little is known about its anticancer effect. In this study, the anti-proliferative and apoptosis mechanisms of BA-β-CD on human breast cancer MCF-7 cells were further investigated. Experimental results confirmed that the complexation model inhibited the growth of MCF-7 cells in a dose-dependent manner, arrested cell cycle in the G2/M phase and induced apoptosis via the mitochondria transduction pathway. Gene and protein analyses showed that the complexation model significantly inhibited Bcl-2 expression and promoted Bax expression, causing caspase-3 and caspase-9 cascade activation. These findings corroborated evidence on microencapsulated BA as an apoptosis inducer in MCF-7 cells. Thus, sour jujube fruits may have potential use as a breast cancer chemotherapeutic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Betulinic Acid
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / physiopathology*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Drug Compounding
  • Female
  • Fruit / chemistry
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Pentacyclic Triterpenes
  • Plant Extracts / pharmacology*
  • Signal Transduction / drug effects
  • Triterpenes / pharmacology*
  • Ziziphus / chemistry*

Substances

  • Pentacyclic Triterpenes
  • Plant Extracts
  • Triterpenes
  • Caspase 3
  • Caspase 9
  • Betulinic Acid